The New Cardio-Oncology Frontier in Hematologic Cancers: Cardiovascular Toxicities of CAR-T Cells and Bispecific T-Cell Engagers

Chimeric antigen receptor T-cell therapy and bispecific T-cell engagers have transformed treatment of relapsed and refractory hematologic malignancies, achieving unprecedented response rates. However, their clinical adoption has revealed a complex spectrum of cardiovascular toxicities, differing in frequency and pattern between the two technologies. Manifestations range from common hemodynamic perturbations—hypotension and tachycardia—to severe events, including malignant arrhythmias, left ventricular dysfunction, myocardial infarction, and cardiogenic shock. These complications seem to have different pathophysiological pathways that are yet to be completely understood: on the one hand, they are frequently intertwined with cytokine release syndrome, the hallmark immune complication of T-cell-redirecting therapies, as seen with chimeric antigen receptor T-cell therapy; on the other, a substantial proportion of cardiovascular events—particularly with bispecific T-cell engagers—occur independently of cytokine release syndrome. Proposed cardiotoxic mechanisms include on-target, off-tumor antigen recognition and consequent damage; interleukin-6-driven systemic inflammation; and off-target, off-tumor antigen cross-reactivity. Effective management requires proactive baseline risk stratification, serial cardiac biomarker monitoring, and timely immunosuppressive intervention—primarily tocilizumab—to mitigate cytokine release syndrome-driven injury. Despite rapid clinical expansion, critical gaps remain: long-term cardiovascular outcomes are poorly characterized, validated surveillance protocols are lacking, and cardiovascular endpoints are rarely included in pivotal trials. This narrative review appraises the pathophysiology, clinical spectrum, and management of cardiovascular toxicities associated with these therapies, aiming to define this emerging cardio-oncology frontier, inform multidisciplinary care frameworks and propose a clinical management algorithm.